Aberrant Gamma-Band Oscillations in Mice with Vitamin D Deficiency: Implications on Schizophrenia and its Cognitive Symptoms.

Abstract

Vitamin D plays an essential role in cognitive functions as well as regulating calcium homeostasis and the immune system. Many epidemiological studies have also shown the close relationship between vitamin D deficiency (VDD) and the risk of schizophrenia. Cortical gamma-band oscillations (GBO) are associated with cognitive functions, such as attention and memory. Patients with schizophrenia show abnormal GBO with increased spontaneous GBO and decreased evoked GBO. However, the direct effect of VDD on GBO remains unknown. Parvalbumin interneurons, which predominantly contribute to the generation of GBO, are surrounded by perineuronal nets (PNN). We sought to investigate the associations among VDD, PNN, and GBO. Here, we injected a viral vector (AAV5-DIO-ChR2-eYFP) into the basal forebrain stereotaxically and implanted electrodes for electroencephalogram (EEG). At baseline, the evoked and spontaneous EEG power at the gamma frequency band was measured in 4-month-old male PV-Cre mice. After six and twenty weeks of vitamin D deficient food administration, the power of GBO was measured in the VDD condition. Next, we injected the chondroitinase ABC (ChABC) enzyme into the frontal cortex to eliminate PNN. We found that the VDD group showed decreased power of both optogenetically- and auditory-evoked GBO, whereas the spontaneous GBO increased. Enzymatic digestion of PNN showed similar changes in GBO. Taken together, we suggest that VDD could result in decreased PNN and, consequently, increase the spontaneous GBO and decrease the evoked GBO, reminiscent of the aberrant GBO in schizophrenia. These results show that VDD might increase the risk of schizophrenia and aggravate the cognitive symptoms of schizophrenia.